Polymorphisms in the IL2, IL2RA and IL2RB genes in multiple sclerosis risk

Interleukin (IL)-2/IL-2R signalling promotes proliferation and survival of activated T cells and has an essential non-redundant role in the production of regulatory T cells. Associations with different autoimmune diseases of polymorphisms in a linkage disequilibrium block in which the IL2/IL21 genes map (4q27), and also in genes encoding the IL2RA and IL2RB subunits (located in 10p15 and 22q13, respectively), were identified through genome-wide studies. Polymorphisms in these three genes were studied in 430 multiple sclerosis (MS) patients and in 550 ethnically matched controls from Madrid (Spain). Replication and meta-analysis with results from an independent cohort of 771 MS patients and 759 controls from Andalucía (Spain) confirmed the association of polymorphisms in the IL2RA gene (PMantel-Haenszel, odds ratio (OR) M-H (95% confidence interval, CI) for rs2104286: 0.0001, 0.75 (0.65-0.87); for rs11594656/rs35285258: 0.004, 1.19 (1.06-1.34); for rs41295061: 0.03, 0.77 (0.60-0.98)); showed a trend for association of the IL2/IL21 rs6822844 (P M-H 0.07, OR M-H (95% CI)0.86 (0.73-1.01)), but did not corroborate the association for IL2RB. Regression analyses of the combined Spanish cohort revealed the independence of two IL2RA association signals: rs2104286 and rs11594656/rs35285258. The relevant role of the IL2RA gene on MS susceptibility adds support to its common effect on autoimmune risk and the suggestive association of IL2/IL21 warrants further investigation. © 2010 Macmillan Publishers Limited All rights reserved.Concepción Núñez holds a research contract from Fondo Investigaciones Sanitarias (CA06/0163) and Elena Urcelay works for the Fundación para la Investigación Biomédica-Hospital Clínico San Carlos. This study was supported by grants from: Alfonso Martín Escudero Foundation and Fondo Investigaciones Sanitarias FIS PI07/0353, FIS PI07/0369, PI08/1636 and Plan Nacional PN-SAF2006-02023.Peer Reviewe

Neurologic outcomes of toxic oil syndrome patients 18 years after the epidemic.

Toxic oil syndrome (TOS) resulted from consumption of rapeseed oil denatured with 2% aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to toxic oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to toxic oil 18 years ago and a referent group of 79 adult age- and sex-frequency-matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neurotoxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT), Programa Integrado de Exploracion Neuropsicologica (PIEN), and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to toxic oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency, and auditory digit span were also significantly associated with exposure. Case subjects also had statistically significantly more neuropsychologic symptoms compared with referents. Using quantitative neurologic tests, we found significant adverse central and peripheral neurologic effects in a group of TOS patients 18 years after exposure to toxic oil when compared with a nonexposed referent group. These effects were not documented by standard clinical examination and were found more frequently in women

Foraminiferal events in the Pliensbachian-Toarcian transition at almonacid de la Cuba (Zaragoza, Spain), the complementary reference section of the proposed Toarcian GSSP

This paper reports results from biostratigraphic and quantitative palaeoecological analysis of diversified boreal foraminiferal faunas found in epicontinental shelf carbonates of the Upper Pliensbachian and Lower Toarcian at Almonacid de la Cuba (northeastern Spain). The results reveal step-wise extinction, replacement and renewal events along the Pliensbachian-Toarcian transition, from the uppermost Spinatum Zone to the lowermost Serpentinum Zone. The extinction of typical, long-ranging Lower Jurassic foraminiferal species takes place during this interval, with the highest extinction rate within the Tenuicostatum Zone, Semicelatum Subzone. The most significant renewal event occurs in the Serpentinum Zone, Elegantulum Subzone, with the first appearance of the genus Citharina. European, North African and American basins show similar patterns; the main dissimilarities concern the interpretation of species such as those belonging to the genus Citharina. Quantitative diversity analysis using richness, dominance, parametric and information theory-based measures is considered the best way to detect palaeoecological events in Jurassic foraminiferal assemblages. This analysis allows four palaeoecological episodes (Episodes I-IV) to be distinguished within the studied stratigraphie interval. Episodes I and II indicate stress conditions related to the Late Pliensbachian to Early Toarcian sea-level rise and Episode IV represents environmental stress linked to the Early Toarcian extinction event. A fair coincidence was detected between Episode IV and the first stage of the pronounced negative excursion of δ13C in the Tenuicostatum Zone, Semicelatum Subzone. On the basis of quantitative abundance results, the autecological information of several taxa is refined and distinct ecological strategies and behaviours can be distinguished.Ministerio de Educación y CienciaUniversidad Complutense de MadridDepto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu

Foraminifera from the Pliensbachian-Toarcian boundary at Ariño Section (Teruel, Spain)

Las asociaciones de foraminíferos presentes en las margas y margocalizas del tránsito Pliensbachiense-Toarciense en la Sección de Ariño son ricas en número de ejemplares y diversas en número de taxones, habiéndose extraído para este estudio un total de 6.389 ejemplares asignados a setenta y dos taxones. Los foraminíferos, dominados por la Familia Vaginulinidae (Superfamilia Nodosarioidea, Suborden Lagenina), se encuentran acompañados en las muestras por restos fósiles correspondientes también a faunas marinas de plataforma de salinidad normal como los bivalvos, braquiópodos, briozoos, crinoideos, decápodos, equinoideos, gasterópodos, holoturioideos, ofiuroideos, ostrácodos, serpúlidos, ammonoideos y peces. Desde el punto de vista tafonómico los ejemplares están mayoritariamente resedimentados aunque puntualmente se ha encontrado un ejemplar reelaborado. Los mecanismos de alteración tafonómica que más han afectado a las asociaciones son los rellenos y cementaciones, las recristalizaciones y recubrimientos de carbonatos, y los transportes bioestratinómicos. Las distribuciones estratigráficas de los taxones muestran una marcada homogeneidad en las asociaciones en el límite Pliensbachiense-Toarciense. Por el contrario, a lo largo del tránsito Pliensbachiense-Toarciense se produce de forma escalonada la extinción de una buena parte de los taxones de rango estratigráfico amplio típicos del Pliensbachiense. La tasa mayor de extinción se localiza en la parte superior de la Subzona Semicelatum de la Zona Tenuicostatum del Toarciense. El evento de renovación faunística más importante tiene lugar también en el Toarciense, y en concreto, en la Subzona Elegantulum de la Zona Serpentinum con la aparición del género Citharina. El acmé de Ammobaculites barrowensis Tappan que tiene lugar en la parte superior de la Subzona Semicelatum es considerado como un evento ecoestratigráfico a nivel de la Cuenca Ibérica.Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu

Polymorphisms in the IL2, IL2RA and IL2RB genes in multiple sclerosis risk

Interleukin (IL)-2/IL-2R signalling promotes proliferation and survival of activated T cells and has an essential non-redundant role in the production of regulatory T cells. Associations with different autoimmune diseases of polymorphisms in a linkage disequilibrium block in which the IL2/IL21 genes map (4q27), and also in genes encoding the IL2RA and IL2RB subunits (located in 10p15 and 22q13, respectively), were identified through genome-wide studies. Polymorphisms in these three genes were studied in 430 multiple sclerosis (MS) patients and in 550 ethnically matched controls from Madrid (Spain). Replication and meta-analysis with results from an independent cohort of 771 MS patients and 759 controls from Andalucía (Spain) confirmed the association of polymorphisms in the IL2RA gene (PMantel–Haenszel, odds ratio (OR)M–H (95% confidence interval, CI) for rs2104286: 0.0001, 0.75 (0.65–0.87); for rs11594656/rs35285258: 0.004, 1.19 (1.06–1.34); for rs41295061: 0.03, 0.77 (0.60–0.98)); showed a trend for association of the IL2/IL21 rs6822844 (PM–H=0.07, ORM–H (95% CI)=0.86 (0.73–1.01)), but did not corroborate the association for IL2RB. Regression analyses of the combined Spanish cohort revealed the independence of two IL2RA association signals: rs2104286 and rs11594656/rs35285258. The relevant role of the IL2RA gene on MS susceptibility adds support to its common effect on autoimmune risk and the suggestive association of IL2/IL21 warrants further investigation